This invention relates to bipyridyl compounds, and particularly, to several new substituted 2,2'-bipyridyl compounds and a process for preparing the same.
Pyridine, recognized by its characteristic C.sub.5 H.sub.5 N formula, has been known for many years and is the parent ring system of a large number of naturally occurring products and important industrial, pharmaceutical and agricultural chemicals. It is an aromatic compound and, much like benzene, gives rise to a large number of substituted homologs and derivatives, many of which are found in the light- and middle-oil fractions of coal tar and are commonly known as pyridine bases.
Bipyridyls, generally categorized by their 2,2'-, 3,3'- and 4,4'-connections, are one such group of pyridine homologs and derivatives and have themselves been generally known to the art for many years. Various of the substituted bipyridyl compounds have long been available and recognized at least in recent years as valuable chelating agents for a variety of metal ions, an example being an article by P. E. Rosevear and W. H. F. Sasse entitled "The Synthesis of Some 4,4',4"-trialkyl-2,2':6',2"-terpyridyls (1,2)" appearing in The Journal of Heterocyclic Chemistry, vol. 8, issue 3, pages 483-5 (1971).
The preparation of such prior art bipyridyl compounds has been accomplished by one of several methods, the most common being refluxing pyridine in the presence of various catalytic agents. One such recognized and useful catalyst for the preparation of bipyridyl compounds from pyridine and its substituted derivatives is generally identified as Raney nickel. References to such catalytic reactions can be found in articles entitled: (1) "Synthetic Applications of Activated Metal Catalysts. Part XII. The Preparation of Symmetrically Substituted 2,2' Bipyridyls." by W. H. F. Sasse and C. P. Wittle, appearing in the J. Chem. Soc., pages 1347-50 (1961); and (2) "Synthetic Applications of Activated Metal Catalysts. Part II. The Formation of Heterocyclic Diaryls." by G. M. Badger and W. H. F. Sasse, appearing in the J. Chem. Soc., pages 616-20 (1956). A second recognized catalyst for accomplishing such bipyridyl formation is a palladium-on-carbon catalyst, commonly referred to as Pd/C. Reference to such Pd/C catalytic reactions can also be found in the 1971 article listed above in The Journal of Heterocyclic Chemistry.
Major problems, however, are encountered when working with these catalytic agents. First, the initial cost of such agents is often prohibitively high. Second, the reaction times are substantially long thus adding to the overall cost in both time and money of the bipyridyl preparations. Third, after a certain period of use, these catalytic agents become spent and must be reactivated often at significant expense in terms of both money and lost preparation time.
A second possible prior art method for the preparation of substituted bipyridyl compounds is generally referred to as the Ullmann reaction, as mentioned briefly in a 1956 article entitled "The Preparation of Some Substituted 2,6-Bis-(2-pyridyl)-pyridines" by F. H. Case and T. J. Casper, appearing in J. Am. Chem. Soc., vol. 78, pages 5842-4 (1956). Specifically, the Ullmann reaction consists of several steps. The first step includes forming substituted 2-bromopyridine by reacting substituted 2-aminopyridine in the presence of sodium nitrite and hydrogen bromide. The second step includes forming the substituted 2,2'-bipyridyl by heating the substituted 2-bromopyridine with a copper or copper bronze powder. The third step includes separating the desired end product.
The Ullmann reaction, however, is not desirable or suitable for effective bipyridyl formation because it requires three distinct steps and even then, only results in low yields. After first obtaining the 2-aminopyridine, it has to be reacted in an involved and controlled two-step process just to form the bipyridyl compound. Then, isolation and recovery of the bipyridyl product is often complicated and costly.
It has also long been known that some coupling, i.e., bipyridyl formation, occurs as one of several side reactions that takes place in the amination process of pyridine and its substituted derivatives. Specifically, amination is generally achieved by means of the long-accepted Tschitschibabin reaction in which pyridine, or one of its alkyl derivatives, is heated with an amount of sodamide in the presence of boiling toluene or an appropriate dialkylaniline. The main product of the amination process is 2-aminopyridine, or a substituted 2-aminopyridine, as spelled out in Leffler, Organic Reactions, vol. I, chapter 4 (1942), entitled "Amination of Heterocyclic Bases by Alkali Amides."
In his work, Leffler specifically discusses the side coupling reaction on pages 95 and 96 in vol. I, Chap. 4, stating that "[b]ipyridyls are also produced in the preparation of aminopyridine." He further states that such side reaction products are often formed in significant quantities when hydrocarbon solvents are employed and that they may undergo amination if the conditions of reaction are sufficiently strenuous, particularly if in the presence of boiling xylene. In this regard, "significant quantities" is not defined or referenced in Leffler's work; but it is apparent from Leffler's treatment that the bipyridyl formed remains merely a byproduct produced in one of various side reactions that take place during the primary amination process.
In an article entitled "Amination in the Heterocyclic Series by Sodium Amide" by R. Norris Shreve, E. H. Riechers, Harry Rubenkoenig and A. H. Goodman, Ind. Eng. Chem., 32, 173 (1940), cited as a reference in Leffler's treatise, 4,4'-dipyridyl is disclosed as only one of a few other nitrogen-containing compounds which were isolated from the diaminopyridine mother liquor. In this context, "dipyridyl" and "bipyridyl" are equivalent terms for all practical purposes and shall be treated as such for the remainder of the present application.
Another reference in Leffler is F. W. Bergstrom and W. Conard Fernelius, Chem. Rev., 12, 156 (1933), which states only that a "large excess of pyridine," when combined with potassium amide at room temperature, "results in the formation, in poor yield, of a soluble blue-colored mono-potassium salt of a partly reduced 4,4'-dipyridyl" with "[v]ery little or no [formation of] 2-aminopyridine . . . "
From analysis of the above prior art references cited by Leffler, it is reasonable to conclude that Leffler's "significant quantities" of bipyridyl formation during the amination of pyridine and its substituted alkylpyridine derivatives, in the presence of either sodium or potassium amide, remain "in poor yield" as shown by F. W. Bergstrom and W. Conard Fernelius, even when large excesses of pyridine or its derivatives are reacted. This prior art amination process was thus known to be an ineffective and impractical method for producing high yields of bipyridyl compounds. Moreover, such processes often present major difficulties in separation and recovery of the small amount of desired bipyridyl from the reaction mixture.
Therefore, as evidenced by the various prior art references discussed herein, of the several methods for forming such bipyridyl compounds known to the art, no known method or process provides an efficient and practical way to prepare effective and substantial yields of these bipyridyls suitable for commercial application.